Microgreens on the rise: Expanding our horizons from farm to fork.

Escalating public health concerns necessitate innovative approaches to food sources. Microgreens, nutrient-rich seedlings of vegetables and herbs, have gained recognition as functional foods. This review explores the evolution of microgreens, cultivation methods, biochemical changes during germination, nutritional content, health benefits, and commercial significance. Comprehensive studies have demonstrated that microgreens have an elevated level of various nutrients. Further, in vitro and in vivo research validated their antioxidant, anticancer, antibacterial, anti-inflammatory, anti-obesity, and antidiabetic properties. Microgreens, termed "desert food," show promise for sustainable food production in climate-vulnerable regions. This paper synthesizes recent research on microgreens, addressing challenges and gaps in understanding their nutritional content and health benefits. It contributes valuable insights for future research, fostering sustainable agriculture and enhancing understanding of microgreens in human health and nutrition.

Circulating metabolites associated with tumor hypoxia and early response to treatment in bevacizumab-refractory glioblastoma after combined bevacizumab and evofosfamide.

Glioblastomas (GBM) are the most common and aggressive form of primary malignant brain tumor in the adult population, and, despite modern therapies, patients often develop recurrent disease, and the disease remains incurable with median survival below 2 years. Resistance to bevacizumab is driven by hypoxia in the tumor and evofosfamide is a hypoxia-activated prodrug, which we tested in a phase 2, dual center (University of Texas Health Science Center in San Antonio and Dana Farber Cancer Institute) clinical trial after bevacizumab failure. Tumor hypoxic volume was quantified by 18F-misonidazole PET. To identify circulating metabolic biomarkers of tumor hypoxia in patients, we used a high-resolution liquid chromatography-mass spectrometry-based approach to profile blood metabolites and their specific enantiomeric forms using untargeted approaches. Moreover, to evaluate early response to treatment, we characterized changes in circulating metabolite levels during treatment with combined bevacizumab and evofosfamide in recurrent GBM after bevacizumab failure. Gamma aminobutyric acid, and glutamic acid as well as its enantiomeric form D-glutamic acid all inversely correlated with tumor hypoxia. Intermediates of the serine synthesis pathway, which is known to be modulated by hypoxia, also correlated with tumor hypoxia (phosphoserine and serine). Moreover, following treatment, lactic acid was modulated by treatment, likely in response to a hypoxia mediated modulation of oxidative vs glycolytic metabolism. In summary, although our results require further validation in larger patients' cohorts, we have identified candidate metabolic biomarkers that could evaluate the extent of tumor hypoxia and predict the benefit of combined bevacizumab and evofosfamide treatment in GBM following bevacizumab failure.

Inhibition of mitochondrial complex I reverses NOTCH1-driven metabolic reprogramming in T-cell acute lymphoblastic leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is commonly driven by activating mutations in NOTCH1 that facilitate glutamine oxidation. Here we identify oxidative phosphorylation (OxPhos) as a critical pathway for leukemia cell survival and demonstrate a direct relationship between NOTCH1, elevated OxPhos gene expression, and acquired chemoresistance in pre-leukemic and leukemic models. Disrupting OxPhos with IACS-010759, an inhibitor of mitochondrial complex I, causes potent growth inhibition through induction of metabolic shut-down and redox imbalance in NOTCH1-mutated and less so in NOTCH1-wt T-ALL cells. Mechanistically, inhibition of OxPhos induces a metabolic reprogramming into glutaminolysis. We show that pharmacological blockade of OxPhos combined with inducible knock-down of glutaminase, the key glutamine enzyme, confers synthetic lethality in mice harboring NOTCH1-mutated T-ALL. We leverage on this synthetic lethal interaction to demonstrate that IACS-010759 in combination with chemotherapy containing L-asparaginase, an enzyme that uncovers the glutamine dependency of leukemic cells, causes reduced glutaminolysis and profound tumor reduction in pre-clinical models of human T-ALL. In summary, this metabolic dependency of T-ALL on OxPhos provides a rational therapeutic target.

Novel Strategy for Untargeted Chiral Metabolomics using Liquid Chromatography-High Resolution Tandem Mass Spectrometry.

Stereospecific recognition of metabolites plays a significant role in the detection of potential disease biomarkers thereby providing new insights in diagnosis and prognosis. D-Hdroxy/amino acids are recognized as potential biomarkers in several metabolic disorders. Despite continuous advances in metabolomics technologies, the simultaneous measurement of different classes of enantiomeric metabolites in a single analytical run remains challenging. Here, we develop a novel strategy for untargeted chiral metabolomics of hydroxy/amine groups (-OH/-NH2) containing metabolites, including all hydroxy acids (HAs) and amino acids (AAs), by chiral derivatization coupled with liquid chromatography-high resolution tandem mass spectrometry (LC-HR-MS/MS). Diacetyl-tartaric anhydride (DATAN) was used for the simultaneous derivatization of-OH/-NH2 containing metabolites as well as the resulting diastereomers, and all the derivatized metabolites were resolved in a single analytical run. Data independent MS/MS acquisition (DIA) was applied to positively identify DATAN-labeled metabolites based on reagent specific diagnostic fragment ions. We discriminated chiral from achiral metabolites based on the reversal of elution order of D and L isomers derivatized with the enantiomeric pair (±) of DATAN in an untargeted manner. Using the developed strategy, a library of 301 standards that consisted of 214 chiral and 87 achiral metabolites were separated and detected in a single analytical run. This approach was then applied to investigate the enantioselective metabolic profile of the bone marrow (BM) and peripheral blood (PB) plasma samples from patients with acute myeloid leukemia (AML) at diagnosis and following completion of the induction phase of chemotherapeutic treatment. The sensitivity and selectivity of the developed method enabled the detection of trace levels of the D-enantiomer of HAs and AAs in primary plasma patient samples. Several of these metabolites were significantly altered in response to chemotherapy. The developed LC-HR-MS method entails a valuable step forward in chiral metabolomics.

The RNA-binding protein SERBP1 functions as a novel oncogenic factor in glioblastoma by bridging cancer metabolism and epigenetic regulation.

BACKGROUND: RNA-binding proteins (RBPs) function as master regulators of gene expression. Alterations in RBP expression and function are often observed in cancer and influence critical pathways implicated in tumor initiation and growth. Identification and characterization of oncogenic RBPs and their regulatory networks provide new opportunities for targeted therapy. RESULTS: We identify the RNA-binding protein SERBP1 as a novel regulator of glioblastoma (GBM) development. High SERBP1 expression is prevalent in GBMs and correlates with poor patient survival and poor response to chemo- and radiotherapy. SERBP1 knockdown causes delay in tumor growth and impacts cancer-relevant phenotypes in GBM and glioma stem cell lines. RNAcompete identifies a GC-rich region as SERBP1-binding motif; subsequent genomic and functional analyses establish SERBP1 regulation role in metabolic routes preferentially used by cancer cells. An important consequence of these functions is SERBP1 impact on methionine production. SERBP1 knockdown decreases methionine levels causing a subsequent reduction in histone methylation as shown for H3K27me3 and upregulation of genes associated with neurogenesis, neuronal differentiation, and function. Further analysis demonstrates that several of these genes are downregulated in GBM, potentially through epigenetic silencing as indicated by the presence of H3K27me3 sites. CONCLUSIONS: SERBP1 is the first example of an RNA-binding protein functioning as a central regulator of cancer metabolism and indirect modulator of epigenetic regulation in GBM. By bridging these two processes, SERBP1 enhances glioma stem cell phenotypes and contributes to GBM poorly differentiated state.

Enzyme-mediated depletion of serum l-Met abrogates prostate cancer growth via multiple mechanisms without evidence of systemic toxicity.

Extensive studies in prostate cancer and other malignancies have revealed that l-methionine (l-Met) and its metabolites play a critical role in tumorigenesis. Preclinical and clinical studies have demonstrated that systemic restriction of serum l-Met, either via partial dietary restriction or with bacterial l-Met-degrading enzymes exerts potent antitumor effects. However, administration of bacterial l-Met-degrading enzymes has not proven practical for human therapy because of problems with immunogenicity. As the human genome does not encode l-Met-degrading enzymes, we engineered the human cystathionine-γ-lyase (hMGL-4.0) to catalyze the selective degradation of l-Met. At therapeutically relevant dosing, hMGL-4.0 reduces serum l-Met levels to >75% for >72 h and significantly inhibits the growth of multiple prostate cancer allografts/xenografts without weight loss or toxicity. We demonstrate that in vitro, hMGL-4.0 causes tumor cell death, associated with increased reactive oxygen species, S-adenosyl-methionine depletion, global hypomethylation, induction of autophagy, and robust poly(ADP-ribose) polymerase (PARP) cleavage indicative of DNA damage and apoptosis.

Identification of a synergistic combination of dimethylaminoparthenolide and shikonin alters metabolism and inhibits proliferation of pediatric precursor-B cell acute lymphoblastic leukemia.

Exploiting metabolic vulnerabilities of cancer cells with nontoxic, plant derived compounds constitutes a novel strategy for both chemoprevention and treatment. A high-throughput screening approach was used to evaluate a library of natural products to determine the most synergistic combination in precursor-B cell acute lymphoblast leukemia. Dimethylaminoparthenolide and shikonin effectively inhibited proliferation resulting in cell death in primary and immortalized leukemia cells, while having negligible effects on normal cells. Dimethylaminoparthenolide and shikonin have been shown separately to inhibit cell survival and proliferative signaling and activate tumor suppressors and proapoptotic pathways. Untargeted metabolomics and metabolic flux analysis with stable isotopically labeled glucose and glutamine exhibited a global shift in metabolism following treatment. Pathway analysis indicated significant differences in amino acid, antioxidant, tricarboxylic acid cycle, and nucleotide metabolism. Together, dimethylaminoparthenolide and shikonin reduced the shunting of glycolytic intermediates into the pentose phosphate pathway for biosynthetic purposes. Similarly, the incorporation of glutamine and glutamine-derived metabolites into purine and pyrimidine synthesis was inhibited by the combination of dimethylaminoparthenolide and shikonin, effectively impeding biosynthetic pathways critical for leukemia cell survival. This approach demonstrates that a synergistic pair of compounds with malignant cell specificity can effectively target metabolic pathways crucial to leukemia cell proliferation and induce apoptosis.

Stable Isotope Dilution LC-HRMS Assay To Determine Free SN-38, Total SN-38, and SN-38G in a Tumor Xenograft Model after Intravenous Administration of Antibody-Drug Conjugate (Sacituzumab Govitecan).

Antibody-drug conjugates (ADCs) have gained significant interest over the past few years due to their targeted delivery, higher efficacy, decreased toxicity and improved therapeutic index over conventional anticancer therapies. Sacituzumab govitecan (SG) is an ADC composed of a Trop-2-targeted antibody conjugated to the cytotoxic payload SN-38. SG is currently being evaluated in clinical trials of several solid cancers. In this nonclinical study, we have developed a highly sensitive and selective approach to measure free and total SN-38 and its glucuronidation metabolite (SN-38G) using stable isotope dilution (SID) ultrahigh-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS). An efficient and fast hydrolysis procedure (2 h at 100 °C) was established to release SN-38, conjugated to the antibody by carbonate linkage. The assay involves the extraction of free SN-38, SN-38G by protein precipitation, and subsequent acid hydrolysis of the protein layer to release antibody-bound SN-38. The developed UHPLC-HRMS method resulted in good linearity (r2 ≥ 0.997), accuracy (RE ≤ ± 9.1%), precision (CVs ≤ 7.7%), and extraction recoveries (85.6-109.3%). The validated method was applied in the plasma and tumor of mice bearing human brain (U251) and breast (MDA-MB-468) tumor xenografts treated with a single dose (0.5 mg) of SG for 6 h. Results revealed the presence of trace level of SN-38G and free SN-38 in plasma, which suggests an improved therapeutic index of SG. The established method makes a significant contribution to the assessment of SG in different cancers.

Foliar Application of Iron Fortified Bacteriosiderophore Improves Growth and Grain Fe Concentration in Wheat and Soybean.

Iron (Fe) is one of the key micronutrients essential for plant growth, yield and quality. Wheat (Triticum aestivum) and soybean (Glycine max) are important food crops but have relatively low Fe content in grains/seeds. Foliar application of Fe-invigorated bacteriosiderophore might increase Fe content in grain as well as improve overall plant growth. From a preliminary experiment conducted on soybean using 20 bacterial strains, Arthrobacter sp. (low siderophore producing) and Lysinibacillus fusiformis (high siderophore producing) were selected based on amount of siderophore produced and response of plants. This result was validated on field grown soybean and wheat crops by applying bacteriosiderophore with or without Fe on foliage. Siderophore was applied at flowering stage in both crops and observations were recorded on the sixth day after foliar spray. Significantly higher shoot biomass, area of leaves or flag leaf and tissue Fe concentration was recorded by siderophore produced by L. fusiformis with Fe as compared to Arthrobacter sp. In comparison to control (water), application of Fe fortified bacterial siderophore resulted not only in increased grain yield by 45% and 28% in wheat and soybean, respectively but also enhanced Fe concentration in grains by 1.7-fold in soybean to 2.0-fold in wheat. Partitioning of Fe in grain was higher in wheat as compared to soybean after foliar spray. Thus, we reported for the first time that bacteriosiderophore with added Fe as foliar application could be an economical and targeted agronomic approach towards Fe fortification in crop plants.

Genome-wide identification and characterization of gene family for RWP-RK transcription factors in wheat (Triticum aestivum L.).

RWP-RKs represent a small family of transcription factors (TFs) that are unique to plants and function particularly under conditions of nitrogen starvation. These RWP-RKs have been classified in two sub-families, NLPs (NIN-like proteins) and RKDs (RWP-RK domain proteins). NLPs regulate tissue-specific expression of genes involved in nitrogen use efficiency (NUE) and RKDs regulate expression of genes involved in gametogenesis/embryogenesis. During the present study, using in silico approach, 37 wheat RWP-RK genes were identified, which included 18 TaNLPs (2865 to 7340 bp with 4/5 exons), distributed on 15 chromosomes from 5 homoeologous groups (with two genes each on 4B,4D and 5A) and 19 TaRKDs (1064 to 5768 bp with 1 to 6 exons) distributed on 12 chromosomes from 4 homoeologous groups (except groups 1, 4 and 5); 2-3 splice variants were also available in 9 of the 37 genes. Sixteen (16) of these genes also carried 24 SSRs (simple sequence repeats), while 11 genes had targets for 13 different miRNAs. At the protein level, MD simulation analysis suggested their interaction with nitrate-ions. Significant differences were observed in the expression of only two (TaNLP1 and TaNLP2) of the nine representative genes that were used for in silico expression analysis under varying levels of N at post-anthesis stage (data for other genes was not available for in silico expression analysis). Differences in expression were also observed during qRT-PCR, when expression of four representative genes (TaNLP2, TaNLP7, TaRKD6 and TaRKD9) was examined in roots and shoots of seedlings (under different conditions of N supply) in two contrasting genotypes which differed in NUE (C306 with low NUE and HUW468 with high NUE). These four genes for qRT-PCR were selected on the basis of previous literature, level of homology and the level of expression (in silico study). In particular, the TaNLP7 gene showed significant up-regulation in the roots and shoots of HUW468 (with higher NUE) during N-starvation; this gene has already been characterized in Arabidopsis and tobacco, and is known to be involved in nitrate-signal transduction pathway.

Differential response of hexaploid and tetraploid wheat to interactive effects of elevated [CO2] and low phosphorus.

KEY MESSAGE: Hexaploid wheat is more responsive than tetraploid to the interactive effects of elevated [CO2] and low P in terms of carboxylate efflux, enzyme activity and gene expression (TaPT1 and TaPAP). Availability of mineral nutrients to plants under changing climate has become a serious challenge to food security and economic development. An understanding of how elevated [CO2] influences phosphorus (P) acquisition processes at the whole-plant level would be critical in selecting cultivars as well as to maintain optimum yield in limited-P conditions. Wheat (Triticum aestivum and T. durum) grown hydroponically with sufficient and low P concentration were exposed to elevated and ambient [CO2]. Improved dry matter partitioning towards root resulted in increased root-to-shoot ratio, root length, volume, surface area, root hair length and density at elevated [CO2] with low P. Interaction of low P and [CO2] induced activity of enzymes (phosphoenolpyruvate carboxylase, malate dehydrogenase and citrate synthase) in root tissue resulting in twofold increase in carboxylates and acid phosphatase exudation. Physiological absorption capacity of roots showed that plants alter their uptake kinetics by increasing affinity (low Km) in response to elevated [CO2] under low P supply. Increased relative expression of genes, purple acid phosphatase (TaPAP) and high-affinity Pi transporter (TaPT1) in roots induced by elevated [CO2] and low P supported our physiological observations. Hexaploid wheat (PBW-396) being more responsive to elevated [CO2] at low P supply as compared to tetraploid (PDW-233) necessitates the ploidy effect to be explored further which might be advantageous under changing climate.

ROS is the major player in regulating altered autophagy and lifespan in sin-3 mutants of C. elegans.

SIN3, a transcriptional corepressor has been implicated in varied functions both as transcription activator and repressor. Recent studies associated Sin3 with the macroautophagic/autophagic process as a negative regulator of Atg8 and Atg32. Though the role of SIN3 in autophagy is being explored, little is known about the overall effect of SIN3 deletion on the survival of an organism. In this study using a Caenorhabditis elegans sin-3(tm1279);him-5(e1490) strain, we demonstrate that under in vivo conditions SIN-3 differentially modulates autophagy and lifespan. We provide evidence that the enhanced autophagy and decreased lifespan observed in sin-3 deletion mutants is dependent on ROS and intracellular oxidative stress. Inability of the mutant worms to maintain redox balance along with dysregulation of enzymatic antioxidants, depletion of GSH and NADP reserves and elevation of ROS markers compromises the longevity of the worms. It is possible that the enhanced autophagic process observed in sin-3(tm1279);him-5(e1490) worms is required to compensate for oxidative stress generated in these worms. ABBREVIATIONS: cat: catalase; DCFDA: 2',7'-dichlorodihydrofluoroscein diacetate; GSH: reduced glutathione; GSSG: oxidized glutathione; H2O2: hydrogen peroxide; HDAC: Histone deacetylase; HID: HDAC interacting domain; him-5: high incidence of males; HLH-30: Helix Loop Helix-30; HNE: 4-hydroxyl-2-noneal; LIPL: LIPase Like; MDA: malondialdehyde; NGM: nematode growth medium; PAH: paired amphipathic α-helix; PE: phosphatidylethanolamine; RFU: relative fluorescence unit; ROS: reactive oxygen species; sin-3/SIN3: yeast Switch Independent; SOD: superoxide dismutase; NADP: nicotinamide adenine dinucleotide phosphate; SQST-1: SeQueSTosome related-1; ATG: AuTophaGy related.

Metabolomic signature of brain cancer.

Despite advances in surgery and adjuvant therapy, brain tumors represent one of the leading causes of cancer-related mortality and morbidity in both adults and children. Gliomas constitute about 60% of all cerebral tumors, showing varying degrees of malignancy. They are difficult to treat due to dismal prognosis and limited therapeutics. Metabolomics is the untargeted and targeted analyses of endogenous and exogenous small molecules, which charact erizes the phenotype of an individual. This emerging "omics" science provides functional readouts of cellular activity that contribute greatly to the understanding of cancer biology including brain tumor biology. Metabolites are highly informative as a direct signature of biochemical activity; therefore, metabolite profiling has become a promising approach for clinical diagnostics and prognostics. The metabolic alterations are well-recognized as one of the key hallmarks in monitoring disease progression, therapy, and revealing new molecular targets for effective therapeutic intervention. Taking advantage of the latest high-throughput analytical technologies, that is, nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS), metabolomics is now a promising field for precision medicine and drug discovery. In the present report, we review the application of metabolomics and in vivo metabolic profiling in the context of adult gliomas and paediatric brain tumors. Analytical platforms such as high-resolution (HR) NMR, in vivo magnetic resonance spectroscopic imaging and high- and low-resolution MS are discussed. Moreover, the relevance of metabolic studies in the development of new therapeutic strategies for treatment of gliomas are reviewed.

Nitrogen-regulated changes in total amino acid profile of maize genotypes having contrasting response to nitrogen deficit.

Sustainable development of cellular organisms depends on a precise coordination between the carbon and nitrogen metabolisms within the living system. Inorganic N is assimilated into amino acids which serve as an important N source for various regulatory metabolic pathways in plants. This study investigates the role of amino acids in C/N balance by examining changes in amino acid profile in the leaves and roots of low-N-tolerant (PHEM-2) and low-N-sensitive (HM-4) maize genotypes grown hydroponically under N-sufficient (4.5 mM), N-deficient (0.05 mM) and N-restoration conditions. N application effectively altered the level of cysteine, methionine, asparagine, arginine, phenylalanine, glycine, glutamine, aspartate and glutamate in both genotypes. Under low N (0.05 mM), the asparagine and glutamine contents increased, while those of glutamate, phenylalanine and aspartate decreased in both genotypes. However, serine content increased in PHEM-2 but decreased in HM-4. Resupply of N to low-N-grown plants of both genotypes restored the amino acids level to that in the control; the restoration was quicker and more consistent in PHEM-2 than in HM-4. Based on alteration of amino acid level, a strategy can be developed to improve the ability of maize to adapt to low-N environments by way of an improved N utilization.

Rapid screening and quantitative determination of bioactive compounds from fruit extracts of Myristica species and their in vitro antiproliferative activity.

Efficient and sensitive LC-MS/MS methods have been developed for the rapid screening and determination of bioactive compounds in different fruit parts of four Myristica species, viz., Myristica beddomeii, Myristica fragrans, Myristica fatua and Myristica malabarica. Twenty-one compounds were identified and characterized on the basis of their accurate mass and MS/MS fragmentation pattern using HPLC-QTOF-MS/MS and NMR analysis. Quantitative determination of five major bioactive compounds was performed using multiple-reaction monitoring mode with continuous polarity switching by UHPLC-QqQLIT-MS/MS. Moreover, in vitro antiproliferative activity of these Myristica species was evaluated against five human cancer cell lines A549, DLD-1, DU145, FaDu and MCF-7 using SRB assay. Seventeen phytoconstituents were identified and reported for the first time from M. beddomeii and sixteen from M. fatua. Quantification result showed highest total content of five major bioactive compounds in mace of M. fragrans. Evaluation of in vitro antiproliferative activity revealed potent activity in all investigated species except M. fragrans.

High Salinity Induces Different Oxidative Stress and Antioxidant Responses in Maize Seedlings Organs.

Salinity negatively affects plant growth and causes significant crop yield losses world-wide. Maize is an economically important cereal crop affected by high salinity. In this study, maize seedlings were subjected to 75 mM and 150 mM NaCl, to emulate high soil salinity. Roots, mature leaves (basal leaf-pair 1,2) and young leaves (distal leaf-pair 3,4) were harvested after 3 weeks of sowing. Roots showed the highest reduction in biomass, followed by mature and young leaves in the salt-stressed plants. Concomitant with the pattern of growth reduction, roots accumulated the highest levels of Na(+) followed by mature and young leaves. High salinity induced oxidative stress in the roots and mature leaves, but to a lesser extent in younger leaves. The younger leaves showed increased electrolyte leakage (EL), malondialdehyde (MDA), and hydrogen peroxide (H2O2) concentrations only at 150 mM NaCl. Total antioxidant capacity (TAC) and polyphenol content increased with the increase in salinity levels in roots and mature leaves, but showed no changes in the young leaves. Under salinity stress, reduced ascorbate (ASC) and glutathione (GSH) content increased in roots, while total tocopherol levels increased specifically in the shoot tissues. Similarly, redox changes estimated by the ratio of redox couples (ASC/total ascorbate and GSH/total glutathione) showed significant decreases in the roots. Activities of enzymatic antioxidants, catalase (CAT, EC 1.11.1.6) and dehydroascorbate reductase (DHAR, EC 1.8.5.1), increased in all organs of salt-treated plants, while superoxide dismutase (SOD, EC 1.15.1.1), ascorbate peroxidase (APX, EC 1.11.1.11), glutathione-s-transferase (GST, EC 2.5.1.18) and glutathione reductase (GR, EC 1.6.4.2) increased specifically in the roots. Overall, these results suggest that Na(+) is retained and detoxified mainly in roots, and less stress impact is observed in mature and younger leaves. This study also indicates a possible role of ROS in the systemic signaling from roots to leaves, allowing leaves to activate their defense mechanisms for better protection against salt stress.

Phytochemical Screening of Garcinia travancorica by HPLC-ESI-QTOF Mass Spectrometry and Cytotoxicity Studies of the Major Biflavonoid Fukugiside.

Qualitative screening of multiclass secondary metabolites present in the fruits, leaves and stem bark extracts of Garcinia travancorica was carried out using HPLC-QTOF-MS analysis. Twenty-three compounds were identified in the fruits, leaves and stem bark; including two acids (hydroxycitric acid and hydroxycitric acid lactone), eight biflavonoids (morelloflavone, GB-1, GB-la, GB-2, GB-2a, fukugiside, xanthochymusside and GB-la glucoside), nine xanthones (α-mangostin, γ-mangostin, 1,5-dihydroxy-3-methoxyxanthone, garciniaxanthone E, 4-(I,1-dimethylprop-2-enyl)-1,3,5,8-tetrahydroxy-xanthone, garcinone A, garcinone B, garcinone C and polyanxanthone C) and four polyisoprenylated benzophenones (gambogenone, aristophenone A, garcinol and garciyunnanin A). Cytotoxicity studies of the major biflavonoid fukugiside reported from G. travancorica leaves revealed a dose-dependent cancer cell growth inhibition in A431 and HeLa cells. The antiproliferative effect appears to be due to the ability of fukugiside to induce S-phase arrest and apoptotic cell death. In HeLa cells, fukugiside reduced the expression of MAPKp38 by 26.1% compared with untreated control.

Helicobacter pylori infection and a P53 codon 72 single nucleotide polymorphism: a reason for an unexplained Asian enigma.

AIM: P53, the most commonly mutated tumor suppressor gene in all types of human cancer, is involved in cell cycle arrest and control of apoptosis. Although p53 contains several polymorphic sites, the codon 72 polymorphism is by far more common. There are divergent reports but many studies suggest p53 pro/pro SNP may be associated with susceptibility to developing various cancers in different regions of the world. The present study aimed to find any correlation between H. pylori infection and progression of carcinogenesis, by studying apoptosis and the p53 gene in gastric biopsies from north Indian population. MATERIALS AND METHODS: A total of 921 biopsies were collected and tested for prevalence of H. pylori by rapid urease test (RUT), imprint cytology and histology. Apoptosis was studied by the TUNEL method. Analysis of p53 gene polymorphism at codon 72 was accomplished by PCR using restriction enzyme BstU1. OBSERVATION: Out of 921 samples tested 56.7% (543) were H. pylori positive by the three techniques. The mean apoptotic index (AI) in the normal group was 2.12, while gastritis had the maximum 4.24 followed by gastric ulcer 2.28, gastropathy 2.22 and duodenal ulcer 2.08. Mean AI in cases with gastric cancer (1.72) was less than the normal group. The analysis of p53 72 SNP revealed that p53 (Arg/Arg), (Pro /Arg) variant are higher (40.59% and 33.66%) as compared to p53 pro/pro variant (25.74%) in the healthy population. CONCLUSIONS: The North Indian population harbors Arg or Pro/Arg SNP that is capable of withstanding stress conditions; this may be the reason of low incidence of gastric disease in spite of high infection with H. pylori. There was no significant association with H. pylori infection and AI. However, there is increased apoptosis in gastritis which may occur independent of H. pylori or p53 polymorphism.

Helicobacter pylori and gastric cancer: Indian enigma.

Helicobacter pylori (H. pylori) is a gram negative microaerophilic bacterium which resides in the mucous linings of the stomach. It has been implicated in the causation of various gastric disorders including gastric cancer. The geographical distribution and etiology of gastric cancer differ widely in different geographical regions and H. pylori, despite being labeled as a grade I carcinogen, has not been found to be associated with gastric cancer in many areas. Studies in Asian countries such as Thailand, India, Bangladesh, Pakistan, Iran, Saudi Arabian countries, Israel and Malaysia, have reported a high frequency of H. pylori infection co-existing with a low incidence of gastric cancer. In India, a difference in the prevalence of H. pylori infection and gastric cancer has been noted even in different regions of the country leading to a puzzle when attempting to find the causes of these variations. This puzzle of H. pylori distribution and gastric cancer epidemiology is known as the Indian enigma. In this review we have attempted to explain the Indian enigma using evidence from various Indian studies and from around the globe. This review covers aspects of epidemiology, the various biological strains present in different parts of the country and within individuals, the status of different H. pylori-related diseases and the molecular pathogenesis of the bacterium.

Sulfur starvation and restoration affect nitrate uptake and assimilation in rapeseed.

We analyzed the effect of omission of sulfur (S) from the nutrient solution and then restoration of S-source on the uptake and assimilation of nitrate in rapeseed. Incubation in nutrient solution without S for 1-6 days led to decline in uptake of nitrate, activities, and expression levels of nitrate reductase (NR) and glutamine synthetase (GS). The nitrite reductase (NiR) and glutamate synthase (GOGAT) activities were not considerably affected. There was significant enhancement in nitrate content and decline in sulfate content. Evaluation of amino acid profile under S-starvation conditions showed two- to fourfold enhancement in the contents of arginine, asparagine and O-acetyl-L-serine (OAS), whereas the contents of cysteine and methionine were reduced heavily. When the S-starved plants were subjected to restoration of S for 1, 3, 5, and 7 days, activities and expression levels of NR and GS recovered within the fifth and seventh days of restoration, respectively. Exogenous supply of metabolites (arginine, asparagine, cysteine, glutamine, OAS, and methionine) also affected the uptake and assimilation of nitrate, with a maximum for OAS. These results corroborate the tight interconnection of S-nutrition with nitrate assimilation and that OAS plays a major role in this regulation. The study must be helpful in developing a nutrient-management technology for optimization of crop productivity.